Piperazines

Abstract

Compounds according to general formula (I)are modulators of the SSTR4 receptor and pharmaceutical compositions containing them are useful in the treatment of pain.

1 . A compound according to general formula (I): 
       
         
           
           
               
               
           
         
         wherein
 A1 represents C or N; 
 A2 represents C or N; 
 A3 represents CR7, N, NR7, or O; 
 A4 represents CH, or N; 
 with the proviso that at least one of A1, A2 and A4 represents N, or at least A3 represents N or NR7; 
 R1 and R4 independently of one another represent
 —H; 
 —C 1-6 -alkyl unsubstituted or substituted with one, two, three or four substituents independently of one another selected from —F, —OH, —OCH 3  and —OCF 3 ; 
 —C 3-8 -cycloalkyl, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from —F, —OH, —C 1-6 -alkyl and —O—C 1-6 -alkyl, wherein in each case alkyl is unsubstituted or substituted with one, two or three —F; 
 —C 2-7 -heterocycloalkyl, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from —F, —OH, —C 1-6 -alkyl and —O—C 1-6 -alkyl, wherein in each case alkyl is unsubstituted or substituted with one, two or three —F; 
 -aryl, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from —F, —Cl, —OH, —C 1-6 -alkyl and —O—C 1-6 -alkyl, wherein in each case alkyl is unsubstituted or substituted with one, two or three —F; or 
 -heteroaryl, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from —F, —Cl, —OH, -cyclopropyl unsubstituted, —C 1-6 -alkyl and —O—C 1-6 -alkyl, wherein in each case alkyl is unsubstituted or substituted with one, two or three —F; 
 
 X represents a bond, —C(═O)— or —CR2R3-; 
 Y represents a bond, —C(═O)—, —C(═O)CH 2 —, or —CR5R6-; 
 R2, R3, R5 and R6 independently of one another represent
 —H; or 
 —C 1-6 -alkyl unsubstituted or substituted with one, two, three or four substituents independently of one another selected from —F, —OH, and —OCH 3 ; 
 
 R7 represents
 —H; 
 —F or —Cl; 
 —C 1-6 -alkyl or —O—C 1-6 -alkyl, wherein in each case alkyl is unsubstituted or substituted with one, two or three —F; or 
 —C 3-8 -cycloalkyl, —O—C 3-8 -cycloalkyl, or —CH 2 —C 3-8 -cycloalkyl, wherein in each case cycloalkyl is unsubstituted or substituted with one, two or three —F; 
 
 with the proviso that when A3 represents NR7, R7 represents
 —H; 
 —C 1-6 -alkyl unsubstituted or substituted with one, two or three —F; or 
 —C 3-8 -cycloalkyl or —CH 2 —C 3-8 -cycloalkyl, wherein in each case cycloalkyl is unsubstituted or substituted with one, two or three —F; 
 
 R8 represents
 —H; 
 —F or —Cl; 
 —C 1-6 -alkyl or —O—C 1-6 -alkyl, wherein in each case alkyl is unsubstituted or substituted with one, two, three or four substituents independently of one another selected from —F, —OH, and —OCH 3 ; or 
 —C 3-4 -cycloalkyl or —CH 2 —C 3-4 -cycloalkyl, wherein in each case cycloalkyl is unsubstituted or substituted with one, two, three or four substituents independently of one another selected from —F, —OH, —OCH 3 , and —C 1-6 -alkyl unsubstituted or substituted with one, two or three —F; 
 
 R9, R10 and R11 independently of one another represent —H or —F; 
 R12 and R13 independently of one another represent —H or —C 1-6 -alkyl unsubstituted or substituted with one, two or three —F; or R12 and R13 together with the carbon atom to which they are attached form C 3-6 -cycloalkyl unsubstituted or substituted with one, two or three —F; 
 
         or a physiologically acceptable salt thereof. 
       
     
     
         2 . The compound according to  claim 1 , which has any one of general formulas (II-a) to (II-h): 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         3 . The compound according to  claim 1 , wherein X represents a bond, —C(═O)—, —CH 2 —, or —CH(CH 3 )—. 
     
     
         4 . The compound according to  claim 1 , wherein R1 represents
 —H;   —CH 3 , —CH 2 CH 3 , —CH(CH 3 ) 2 , —CH 2 CH(CH 3 ) 2 , —CH 2 CHF 2 , —CH 2 CF 3 , —CH 2 CF(CH 3 ) 2 , —CH 2 CF 2 CH 3 , —CH 2 CH 2 OCH 3 , —CH 2 C(CH 3 ) 2 OH, or —CH 2 C(CH 3 ) 2 CH 2 OCH 3 ;   -cyclopropyl, -cyclobutyl, or -cyclohexyl; in each case unsubstituted or substituted with one or two substituents independently of one another selected from —F and —CF 3 ;   -oxetanyl or -tetrahydropyranyl; in each case unsubstituted or monosubstituted with —CH 3 ;   -phenyl unsubstituted or monosubstituted with —F or —CF 3 ; or   -pyrazolyl, -pyridinyl, -pyrimidinyl, -pyridazinyl, or -pyrazinyl; in each case unsubstituted or monosubstituted with —CH 3 , —CF 3 , or -cyclopropyl unsubstituted.   
     
     
         5 . The compound according to  claim 1 , wherein Y represents a bond, —C(═O)—, —C(═O)CH 2 —, —CH 2 —, or —CH(CH 3 )—. 
     
     
         6 . The compound according to  claim 1 , wherein R4 represents
 —H;   —CH 3 , CH 2 CH 3 , —CH 2 CH 2 CH 3 , —CH(CH 3 ) 2 , —CH 2 CH(CH 3 ) 2 , —CH 2 CHF 2 , —CH 2 CF 3 , or —CH 2 CH 2 OCH 3 ;   -phenyl unsubstituted;   -cyclopropyl, cyclobutyl or cyclohexyl; in each case unsubstituted or substituted with one or two —F;   -oxetanyl or -tetrahydropyranyl; in each case unsubstituted; or   -pyrazolyl, -oxazolyl, -pyridyl; in each case unsubstituted or monosubstituted with —CH 3 , or —CH(CH 3 ) 2 .   
     
     
         7 . The compound according to  claim 1 , wherein R7 represents —H or —CH 3 . 
     
     
         8 . The compound according to  claim 1 , wherein R8 represents —H, —F, —Cl, —CH 3 , —CF 3 , —OCH 3 , or -cyclopropyl unsubstituted. 
     
     
         9 . The compound according to  claim 1 , wherein R9, R10 and R11 each represent —H; and/or wherein R12 and R13 each represent —CH 3 . 
     
     
         10 . The compound according to  claim 1 , which is selected from the group consisting of
 00 rac-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-1-(pyrimidin-2-ylmethyl)piperazine-2-carboxamide;   002 rac-1-isopropyl-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-piperazine-2-carboxamide;   003 rac-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-1-(pyridin-2-yl-methyl)piperazine-2-carboxamide;   004 rac-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-1-(pyridazin-3-ylmethyl)piperazine-2-carboxamide;   rac-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-1-(pyrimidin-5-ylmethyl)piperazine-2-carboxamide;   006 rac-1- ((1-methyl-1H-pyrazol-3-yl)methyl)-N-(2-(8-methylimidazo [1,5-a]-pyridin-3-yl)propan-2-yl)piperazine-2-carboxamide;   rac-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-1-(pyrazin-2-ylmethyl)piperazine-2-carboxamide;   008 rac-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-1-(pyrimidin-4-ylmethyl)piperazine-2-carboxamide;   rac-1-acetyl-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-piperazine-2-carboxamide;   rac-1-(1-methyl-1H-pyrazole-4-carbonyl)-N-(2-(8-methylimidazo [1,5-a]-pyridin-3-yl)propan-2-yl)piperazine-2-carboxamide;   011 rac-1-(3,3-difluorocyclobutane-1-carbonyl)-N-(2-(8-methylimidazo [1,5-a]-pyridin-3-yl)propan-2-yl)piperazine-2-carboxamide;   012 rac-1-(cyclopropanecarbonyl)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)-propan-2-yl)piperazine-2-carboxamide;   013 rac-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-1-(oxetane-3-carbonyl)piperazine-2-carboxamide;   014 rac-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-1-(oxetan-3-yl-methyl)piperazine-2-carboxamide;   (S)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)piperazine-2-carboxamide;   (S)-1-methyl-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-016 piperazine-2-carboxamide;   (S)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-1-(2,2,2-01 trifluoroethyl)piperazine-2-carboxamide;   018 (S)-1-(2-fluoro-2-methylpropyl)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)piperazine-2-carboxamide;   019 (S)-1-(2,2-difluoropropyl)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)-propan-2-yl)piperazine-2-carboxamide;   (S)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-1- ((1-(trifluoro-methyl)cyclopropyl)methyl)piperazine-2-carboxamide;   021 (S)-1-(3,3-difluorocyclobutyl)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)-propan-2-yl)piperazine-2-carboxamide;   022 (S)-1- ((2-cyclopropylpyridin-4-yl)methyl)-N-(2-(8-methylimidazo [1,5-a]-pyridin-3-yl)propan-2-yl)piperazine-2-carboxamide;   (S)-1-(2-hydroxy-2-methylpropyl)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-023 yl)propan-2-yl)piperazine-2-carboxamide;   02 (S)-1- ((4,4-difluoro-1-methylcyclohexyl)methyl)-N-(2-(8-methyl-imidazo [1,5-a] pyridin-3-yl)propan-2-yl)piperazine-2-carboxamide;   025 (S)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-1-(3-(trifluoro-methyl)benzyl)piperazine-2-carboxamide;   026 (S)-1-(2-fluorobenzyl)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)piperazine-2-carboxamide;   027 (S)-1-(4-fluorobenzyl)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)piperazine-2-carboxamide;   028 (S)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-1-(4-(trifluoro-methyl)benzyl)piperazine-2-carboxamide;   (S)-1-(3-fluorobenzyl)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-029 yl)piperazine-2-carboxamide;   030 (S)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-1- ((6-(trifluoro-methyl)pyridin-3-yl)methyl)piperazine-2-carboxamide;   031 (S)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-1- ((3-methyl-oxetan-3-yl)methyl)piperazine-2-carboxamide;   032 (S)-1-(4,4-difluorocyclohexyl)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)-propan-2-yl)piperazine-2-carboxamide;   033 (S)-1-(cyclobutylmethyl)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)-propan-2-yl)piperazine-2-carboxamide;   (S)-1-isobutyl-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-034 piperazine-2-carboxamide;   035 (S)-1-isopropyl-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-piperazine-2-carboxamide;   036 (S)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-1- ((2-(trifluoro-methyl)pyridin-4-yl)methyl)piperazine-2-carboxamide;   037 (S)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-1- ((4-methyl-tetrahydro-2H-pyran-4-yl)methyl)piperazine-2-carboxamide;   038 (S)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-1- ((2-(trifluoro-methyl)pyrimidin-5-yl)methyl)piperazine-2-carboxamide;   039 (S)-1-(3-methoxy-2,2-dimethylpropyl)-N-(2-(8-methylimidazo [1,5-a]-pyridin-3-yl)propan-2-yl)piperazine-2-carboxamide;   040 (S)-1-isopropyl-N-(2-(7-methyl-1H-indazol-3-yl)propan-2-yl)piperazine-2-carboxamide;   041 (S)-1-ethyl-N-(2-(7-methyl-1H-indazol-3-yl)propan-2-yl)piperazine-2-carboxamide;   042 (S)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-1-(oxetan-3-yl-methyl)piperazine-2-carboxamide;   043 (S)-4-methyl-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-piperazine-2-carboxamide;   044 (S)-4-methyl-1- ((1-methyl-1H-pyrazol-4-yl)methyl)-N-(2-(8-methyl-imidazo [1,5-a] pyridin-3-yl)propan-2-yl)piperazine-2-carboxamide;   045 (S)-4-methyl-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-1-(2,2,2-trifluoroethyl)piperazine-2-carboxamide;   046 (S)-1,4-dimethyl-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-piperazine-2-carboxamide;   047 (S)-4-methyl-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-1-((tetrahydro-2H-pyran-4-yl)methyl)piperazine-2-carboxamide;   048 (S)-4-methyl-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-1-(oxetan-3-ylmethyl)piperazine-2-carboxamide;   049 (S)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-4-(2,2,2-trifluoroethyl)piperazine-2-carboxamide;   050 (S)-4-(2,2-difluoroethyl)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)piperazine-2-carboxamide;   051 (S)-4-(2-methoxyethyl)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)piperazine-2-carboxamide;   052 (S)-4-isopropyl-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-piperazine-2-carboxamide;   053 (S)-4-cyclobutyl-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-piperazine-2-carboxamide;   054 (S)-4-ethyl-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-piperazine-2-carboxamide;   055 (S)-4-(4,4-difluorocyclohexyl)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)-propan-2-yl)piperazine-2-carboxamide;   056 (S)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-4-(tetrahydro-2H-pyran-4-yl)piperazine-2-carboxamide;   057 (S)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-4- ((tetrahydro-2H-pyran-4-yl)methyl)piperazine-2-carboxamide;   058 (S)-4-benzyl-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-piperazine-2-carboxamide;   059 (S)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-4-(pyridin-4-yl-methyl)piperazine-2-carboxamide;   060 (S)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-4-(pyridin-2-yl-methyl)piperazine-2-carboxamide;   061 (S)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-4-(pyridin-3-yl-methyl)piperazine-2-carboxamide;   062 (S)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-4-(oxazol-5-yl-methyl)piperazine-2-carboxamide;   063 (S)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-4-(oxazol-4-yl-methyl)piperazine-2-carboxamide;   064 (S)-4- ((1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl) methyl)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)piperazine-2-carboxamide;   065 (S)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-4-(oxazol-2-yl-methyl)piperazine-2-carboxamide;   066 (S)-4- ((1-methyl-1H-pyrazol-3-yl)methyl)-N-(2-(8-methylimidazo [1,5-a]-pyridin-3-yl)propan-2-yl)piperazine-2-carboxamide;   067 (S)-4- ((4,4-difluorocyclohexyl)methyl)-N-(2-(8-methylimidazo [1,5-a]-pyridin-3-yl)propan-2-yl)piperazine-2-carboxamide;   068 (S)-4-(cyclobutylmethyl)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)-propan-2-yl)piperazine-2-carboxamide;   069 (S)-4-isobutyl-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-piperazine-2-carboxamide;   (S)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-4-propyl-070piperazine-2-carboxamide;   071 (S)-4- ((1-methyl-1H-pyrazol-4-yl)methyl)-N-(2-(8-methylimidazo [1,5-a]-pyridin-3-yl)propan-2-yl)piperazine-2-carboxamide;   072 (S)-4- ((1-methyl-1H-pyrazol-5-yl)methyl)-N-(2-(8-methylimidazo [1,5-a]-pyridin-3-yl)propan-2-yl)piperazine-2-carboxamide;   073 (S)-4- ((1-isopropyl-1H-pyrazol-3-yl)methyl)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)piperazine-2-carboxamide;   074 (S)-4- ((1-isopropyl-1H-pyrazol-4-yl)methyl)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)piperazine-2-carboxamide;   075 (S)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-4-(oxetan-3-yl)piperazine-2-carboxamide;   076 (S)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-4-(oxetan-3-ylmethyl)piperazine-2-carboxamide;   077 (S)-4-(cyclopropanecarbonyl)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)-propan-2-yl)piperazine-2-carboxamide;   078 (S)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-4-(tetrahydro-2H-pyran-4-carbonyl)piperazine-2-carboxamide;   079 (S)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-4-(2-(tetra-hydro-2H-pyran-4-yl)acetyl)piperazine-2-carboxamide;   080 (S)-4-(3,3-difluorocyclobutane-1-carbonyl)-N-(2-(8-methylimidazo [1,5-a]-pyridin-3-yl)propan-2-yl)piperazine-2-carboxamide;   081 (S)-4-(1-isopropyl-1H-pyrazole-4-carbonyl)-N-(2-(8-methylimidazo [1,5-a]-pyridin-3-yl)propan-2-yl)piperazine-2-carboxamide;   082 (S)-4-(1-methyl-1H-pyrazole-5-carbonyl)-N-(2-(8-methylimidazo [1,5-a]-pyridin-3-yl)propan-2-yl)piperazine-2-carboxamide;   083 (S)-4-(1-methyl-1H-pyrazole-4-carbonyl)-N-(2-(8-methylimidazo [1,5-a]-pyridin-3-yl)propan-2-yl)piperazine-2-carboxamide;   084 (S)-4-(1-methyl-1H-pyrazole-3-carbonyl)-N-(2-(8-methylimidazo [1,5-a]-pyridin-3-yl)propan-2-yl)piperazine-2-carboxamide;   085 (S)-1-benzyl-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-piperazine-2-carboxamide;   086 (S)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-1- ((tetrahydro-2H-pyran-4-yl)methyl)piperazine-2-carboxamide;   087 (S)-1- ((4,4-difluorocyclohexyl)methyl)-N-(2-(8-methylimidazo [1,5-a]-pyridin-3-yl)propan-2-yl)piperazine-2-carboxamide;   088 (S)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-1- ((6-methyl-pyridin-3-yl)methyl)piperazine-2-carboxamide;   089 (S)-1- ((3,3-difluorocyclobutyl)methyl)-N-(2-(8-methylimidazo [1,5-a]-pyridin-3-yl)propan-2-yl)piperazine-2-carboxamide;   090 (S)-1- ((1-methyl-1H-pyrazol-4-yl)methyl)-N-(2-(8-methylimidazo [1,5-a]-pyridin-3-yl)propan-2-yl)piperazine-2-carboxamide;   091 (S)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-1- ((2-methyl-pyridin-4-yl)methyl)piperazine-2-carboxamide;   092 (S)-1-(2-methoxyethyl)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)piperazine-2-carboxamide;   093 rac-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-1-phenyl-piperazine-2-carboxamide;   094 (S)-1-methyl-N-(2-(7-methyl-1H-indazol-3-yl)propan-2-yl)piperazine-2-carboxamide;   095 (S)-4-methyl-N-(2-(7-methyl-1H-indazol-3-yl)propan-2-yl)piperazine-2-carboxamide;   096 (S)-N-(2-(7-methyl-1H-indazol-3-yl)propan-2-yl)-1- ((tetrahydro-2H-pyran-4-yl)methyl)piperazine-2-carboxamide;   097 (S)-1-(2-methoxyethyl)-N-(2-(7-methyl-1H-indazol-3-yl)propan-2-yl)-piperazine-2-carboxamide;   098 (S)-N-(2-(7-methyl-1H-indazol-3-yl)propan-2-yl)-1-(2,2,2-trifluoroethyl)-piperazine-2-carboxamide;   099 (S)-4-methyl-N-(2-(1-methyl-1H-indazol-3-yl)propan-2-yl)piperazine-2-carboxamide;   100 (S)-1-methyl-N-(2-(1-methyl-1H-indazol-3-yl)propan-2-yl)piperazine-2-carboxamide;   101 (S)-1-(2-methoxyethyl)-N-(2-(1-methyl-1H-indazol-3-yl)propan-2-yl)-piperazine-2-carboxamide;   102 (S)-N-(2-(1-methyl-1H-indazol-3-yl)propan-2-yl)-1-(2,2,2-trifluoroethyl)-piperazine-2-carboxamide;   103 (S)-N-(2-(1-methyl-1H-indazol-3-yl)propan-2-yl)-1- ((tetrahydro-2H-pyran-4-yl)methyl)piperazine-2-carboxamide;   (S)-N-(2-(8-chloroimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-1-methyl-104 piperazine-2-carboxamide;   105 (S)-N-(2-(8-chloroimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-4-methyl-piperazine-2-carboxamide;   106 (S)-N-(2-(8-chloroimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-1- ((1-methyl-1H-pyrazol-4-yl)methyl)piperazine-2-carboxamide;   107 (S)-N-(2-(8-chloroimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-1- ((3,3-difluorocyclobutyl)methyl)piperazine-2-carboxamide;   108 (S)-N-(2-(8-chloroimidazo [1,5-a] pyridin-3-yl)propan-2-yl)piperazine-2-carboxamide;   109 (R)-N-(2-(8-chloroimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-1-methyl-piperazine-2-carboxamide;   110 (S)-1-methyl-N-(2-(8-(trifluoromethyl)imidazo [1,5-a] pyridin-3-yl)propan-2-yl)piperazine-2-carboxamide;   111 (S)-1- ((1-methyl-1H-pyrazol-4-yl)methyl)-N-(2-(8-(trifluoromethyl)-imidazo [1,5-a] pyridin-3-yl)propan-2-yl)piperazine-2-carboxamide;   112 (S)-4-methyl-N-(2-(8-(trifluoromethyl)imidazo [1,5-a] pyridin-3-yl)propan-2-yl)piperazine-2-carboxamide;   113 (S)-1- ((3,3-difluorocyclobutyl)methyl)-N-(2-(8-(trifluoromethyl)imidazo-[1,5-a] pyridin-3-yl)propan-2-yl)piperazine-2-carboxamide;   114 (S)-N-(2-(1,8-dimethylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-1-methyl-piperazine-2-carboxamide;   115 (S)-1- ((3,3-difluorocyclobutyl)methyl)-N-(2-(1,8-dimethylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)piperazine-2-carboxamide;   116 (S)-N-(2-(1,8-dimethylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-4-methyl-piperazine-2-carboxamide;   117 (S)-N-(2-(1,8-dimethylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-1- ((1-methyl-1H-pyrazol-4-yl)methyl)piperazine-2-carboxamide;   118 (S)-N-(2-(8-cyclopropylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-1-methyl-piperazine-2-carboxamide;   119 (S)-N-(2-(8-cyclopropylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-4-methyl-piperazine-2-carboxamide;   120 (S)-N-(2-(8-cyclopropylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-1- ((1-methyl-1H-pyrazol-4-yl)methyl)piperazine-2-carboxamide;   121 (S)-N-(2-(8-cyclopropylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-1- ((3,3-difluorocyclobutyl)methyl)piperazine-2-carboxamide;   122 (S)-N-(2-(7-methyl-1H-indazol-3-yl)propan-2-yl)-1-(oxetan-3-ylmethyl)-piperazine-2-carboxamide;   123 (S)-N-(2-(1-methyl-1H-indazol-3-yl)propan-2-yl)-1-(oxetan-3-ylmethyl)-piperazine-2-carboxamide;   (S)-1-methyl-N-(2-(7-methylbenzo [d] isoxazol-3-yl)propan-2-yl)piperazine-1242-carboxamide;   125 (S)-N-(2-(8-chloro-[1,2,4] triazolo [4,3-a] pyridin-3-yl)propan-2-yl)-1-methylpiperazine-2-carboxamide;   126 (S)-N-(2-(1,7-dimethyl-1H-indazol-3-yl)propan-2-yl)-1-methylpiperazine-2-carboxamide;   127 (S)-1-(2,2-difluoroethyl)-N-(2-(8-methylimidazo [1,5-a] pyridin-3-yl)propan-2-yl)piperazine-2-carboxamide;   128 (S)-N-(2-(8-methoxyimidazo [1,5-a] pyridin-3-yl)propan-2-yl)-1-methylpiperazine-2-carboxamide; or   129 (S)-N-(2-(7-fluoro-1H-indazol-3-yl)propan-2-yl)-1-methylpiperazine-2-carboxamide;   or a physiologically acceptable salt thereof.   
     
     
         11 . A pharmaceutical composition comprising a compound according to  claim 1 . 
     
     
         12 . A pharmaceutical composition comprising a compound according to  claim 10 . 
     
     
         13 . A method of treating pain in a patient in need thereof, said method comprising administering to said patient an effective amount therefor of at least one compound according to  claim 1 . 
     
     
         14 . A method of treating pain in a patient in need thereof, said method comprising administering to said patient an effective amount therefor of at least one compound according to  claim 10 .